Haemangiomas are formed by cells expressing high levels of alphavbeta3 integrin and lacking acetylated LDL uptake

Haemangiomas are benign tumours occurring in up to 12% of Caucasians, particularly in infancy and childhood. In the present study, two variant cell lines were isolated from murine endothelioma cells. One variant, named t.End.1V(high), represented 16.9% of the parental cell population and was selected by virtue of high expression levels of integrin alphavbeta3 and reduced capacity to endocytose acetylated low-density lipoproteins (Ac-LDLs). A second variant, named t.End.1V(low), represented 38.8% of the parental endothelioma cell line, expressed low levels of alphavbeta3 integrin, and was able to endocytose Ac-LDL. These phenotypic modifications were stable and correlated with specific morphological and functional properties of the two variant cell lines. While the t.End.1V(high) cells induced the formation of large haemangiomas when injected subcutaneously into mice, the t.End.1V(low) cells formed haemangiocytomas. When compared with t.End.1V(low) cells, the t.End.1V(high) cells showed increased migratory capacity, lacked an inflammatory response, and formed cord-like structures in fibrin gels. In contrast, the t.End.1V(low) cells organized into cysts with a lumen in fibrin gels. They rarely formed blood-filled haemangiomas in vivo and recruited host smooth muscle cells, a phenomenon typical for vessel wall maturation of resting cells. These data suggest that Ac-LDL uptake and the level of alphavbeta3 integrin expression are linked to the ability of endothelial cells to form large haemangiomas in vivo.